A leading cause of death in the western world is atherosclerosis. More than thirteen million people in the United States have been diagnosed with this disease with a large number of patients having arteries or veins that have become narrowed and need to be enlarged. Angioplasty, a common technique to enlarge an artery or vein, is an interventional radiologic technique in which a narrowed artery or vein is enlarged with the use of a balloon angioplasty catheter.
To perform an angioplasty, an angiogram is used to obtain a precise image of the narrowed artery or vein. A catheter is inserted into a blood vessel and is guided to the site of the narrowing with an X-ray monitor. A contrast medium is injected through the catheter and a series of X-ray images are obtained to outline the blood vessel. The images obtained from the X-ray are used to identify and measure the abnormal narrowing of the blood vessel. The initial catheter used for diagnostic purposes is then removed and a catheter having an inflatable balloon around its shaft is inserted. The balloon is inflated in the narrowed portion of the vessel to widen the artery or vein. In some cases, a metallic stent is placed within the blood vessel in order to widen the blood vessel.
Although the initial success rate is high, the long-term success rate of angioplasty is unfortunately rather low and a subsequent procedure is often necessary. It has been estimated that nearly 25-45% of the 450,000 coronary angioplasties done in the United States each year fail within the first few months of the operation. Restenosis is defined to be the reclosing of the artery or vein to less than 50% of its original size. Because of restenosis, an additional angioplasty or another procedure, such as bypass surgery, is necessary to reopen the blood vessel. The need for subsequent procedures has a traumatic effect on the patient and on those concerned about the patient's health and additionally greatly increases medical costs. In fact, the cost to the health care system in the United States for subsequent procedures has been estimated to be 2 billion dollars annually.
The problems associated with restenosis are not limited only with an angioplasty procedure but also occur with other coronary revascularization procedures. Restenosis, for instance, is also associated with rotoblator, atherectomy catheters, hot and cold laser catheters, transluminal extraction catheters, and ultrasonic ablation. The magnitude of the problem caused by restenosis is therefore quite extensive.
Restenosis is difficult to prevent since its cause is not completely understood. Restenosis, however, is believed to be primarily caused by intimal hyperplasia and negative remodeling, and, to a lesser extent, elastic recoil. Angioplasty, as well as other revascularization techniques, expose the medial smooth muscle of the blood vessel to circulating mitogenic factors when the artery is dilated. As a result of platelet degranulation, growth factors are released which induce mitogenesis and promote proliferation of cells. Vascular smooth muscle cells consequently migrate into the intima, where they synthesize collagen and elastin, which comprise the bulk of the restenotic lesion.
One approach to combating restenosis is through drug therapy. Some agents tested in restenosis trials include antiplatelet agents, anticoagulants, thromboxane antagonists, prostanoids, calcium channel blockers, ACE inhibitors, antiproliferative growth factor inhibitors, lipid lowering agents, vitamins and antioxidants, and corticosteroids and non-steriodial A. Another agent that has been used to prevent restenosis is hyaluaronic acid. The use of hyaluaronic acid is shown and described in U.S. Pat. No. 5,614,506 to Falk et al., the disclosure of which is incorporated herein. The use of agents to block restenosis has generally been met with failure or at most limited success. The drug trials involving these agents have been fraught with problems such as incomplete angiographic follow-up, variable definitions of restenosis, small sample sizes, and varying drug dosage.
Another approach used to combat is the use of a stent. A polymer stent, for instance, is placed within the treated blood vessel and delivers medicine to the damaged blood vessel. The polymer stent need not be removed since it naturally dissolves after the blood vessel has been repaired. Stents have produced promising results in that they appear to significantly reduce the rate of restenosis by approximately 10%. Studies of stent usage, however, have revealed undesirable side effects, such as an increased incidence of bleeding complications associated with stent implantation. Stents unfortunately are unable to completely eliminate restenosis and a need exists for a treatment method that even further reduces the rate of restenosis.
An emerging and promising treatment for coronary restenosis is intracoronary radiation therapy (ICRT). In general, intracoronary radiation therapy delivers radiation to a damaged area of the blood vessel to prevent restenosis. A delivery catheter allows a radiation source to be delivered to the angioplasty site where it remains for a number of minutes before being withdrawn. The radiation source may be a line or "train" of several miniature cylindrical sealed sources containing a radioactive material, such as Sr-90, Ir-192, I-125, or Re-186. Rather than a train of radiation sources, other irradiation delivery techniques include radioactive seeds or pellets, radioactive wires, intravascular x-ray sources, and liquid-filled balloons emitting particulate or electromagnetic radiation. A radiation source never comes in contact with the patient's tissue or blood and a transfer device shields the radiation from health care workers during its handling. One advantage of intracoronary radiation therapy is that it typically adds less than ten minutes to the total procedure time and is easily incorporated within the cath lab. An example of an intracoronary radiation therapy is shown and described in U.S. Pat. No. 5,683,345 to Waksman et al., the disclosure of which is incorporated herein.
Trials of intracoronary radiation therapy have produced promising results. In one trial, for instance, one-half of a group of patients received gamma radiation and the other half received placebo treatment while all of the patients in this trial had a coronary stent. The preliminary results of the study showed that the treated group had a restenosis rate of 17%, compared with a restenosis rate of 54% in the non-treated group. Intracoronary radiation therapy has also shown to be preferable over the use of a stent. For instance, coronary stents typically produce a late loss index of 25 to 30%, meaning that on average 70 to 75% of the initial improvement in lumen diameter achieved by angioplasty was still present six months later. In contrast, a study involving intracoronary radiation therapy reduced the late loss index to only 5%, meaning that on average 95% of the initial improvement in lumen diameter was still present six months later. When only those patients receiving a higher dosage of radiation were evaluated, the late loss index dropped to zero. This study therefore suggests that with proper dosing level, additional devices or therapies should not be necessary.
The success of the intracoronary radiation therapy trials also point to shortcomings of the therapy. As discussed above, the success of intracoronary radiation therapy depends upon the proper dosage level with dosimetry measured in the sub-millimeter range being essential to optimally prescribing and delivering the radiation to the lesion. Proper dosing is difficult to achieve since it is dependent, among other things, upon the distance between the source of radiation and the lesion and upon the exposure time. Presently, X-ray imaging is used to determine the size of the vessel. The calculation or measurement of the dose-rate at a certain distance from the source is next made to determine the dwell-time required to deliver a certain dose given the vessel size.
Achieving the proper dosing is difficult with conventional methods. Since the imaging techniques used to estimate distances produce two-dimensional images, an accurate distance between the radiation source and the lesion cannot easily be obtained due to possible undetectable differences in location along the third dimension. As a result of errors in estimating the distance, the lesion may not be exposed to the radiation for the correct period of time. The proper dose, moreover, depends upon the lumen size and the wall thickness of the blood vessel, both of which cannot be accurately measured through conventional imaging techniques. Because of inaccuracies in measuring the distance between the source and lesion, the lumen size, and the wall thickness, optimal results with intracoronary radiation therapy are difficult to achieve. Intracoronary radiation therapy therefore cannot be successfully performed in a consistent manner.
Furthermore, conventional radiation treatment planning is less than optimal for this irradiation. A typical radiation treatment plan involves data entry and digitization of anatomical regions and images. The time needed to determine the distance and the dwell-time would delay the immediate treatment of a patient and may be detrimental to the patient's health. A conventional radiation treatment planning system would prevent medical personnel from adjusting or altering their treatment plan before treatment which may be necessary due to unforeseen circumstances discovered during the revascularization technique, such as the lumen size, wall thickness, and other patient specific information. A need therefore exists for a radiation treatment planning system which addresses the shortcomings of conventional treatment planning.
Another difficulty encountered with conventional treatment methods is identifying the position of a catheter within the blood vessel. This difficulty relates both to the position of the catheter along the length of a blood vessel and also pertains to the rotational position of the catheter. In other words, with conventional techniques, it is difficult and at times impossible to know the precise position and orientation of a catheter within the patient's body. This problem of locating a catheter is problematic not only in the treatment of restenosis but is encountered in virtually all uses of a catheter. Furthermore, this problem occurs when assessing the magnitude of a patient's illness, when arriving at a treatment plan, during the treatment of the patient, and also during the verification of a particular treatment.
To illustrate the problem in locating a catheter with conventional techniques, consider a situation in which a patient has a lesion along a particular length of an artery and intracoronary radiation is to be used to treat the lesion. The position of the catheter is first approximately placed at a desired location within the patient and this desired location may be verified with fluoroscopy. U.S. Pat. No. 5,054,492 to Scribner et al., the disclosure of which is incorporated herein by reference, provides one example of how a marker may be placed on a catheter guide and viewed through fluoroscopy in order to verity the location of catheter. The catheter is placed at the approximate position of the distal end of the lesion through the use of an automatic pull-back mechanism. The precise location of the catheter cannot be obtained but the approximate location of the catheter is estimated by calculating the speed of the catheter with the time that it has been moved in order to arrive at the traveled distance. With the catheter at the approximate location of a distal end of the lesion, the lesion is exposed to the radiation source and the dwell-time and dwell-positions of the radiation source or sources is again controlled with the automatic pull-back mechanism by estimating distance from the catheter speed and time of travel. Because of the inherent inaccuracies in indirectly estimating the position of a catheter through the parameters of speed and time, a need exists for systems and methods that allow the position of a catheter to determined more accurately.
Another limitation in catheter technology is that the rotational orientation of the catheter is typically not monitored. As a result, even though a lesion may only be located along one segment of an artery and not along an entire circumference of the lumen wall, the radiation is delivered in all directions in order to ensure that the lesion receives the radiation. Because conventional techniques do not allow the radiation to be directed only to the lesion, the radiation is often needlessly exposed to healthy portions of the artery. A need therefore exists for systems and methods that allow radiation to be focused to only certain segments of the arterial wall.
Even if radiation should be applied to the entire surface of an artery, it is difficult if not impossible to deliver a uniform dose of radiation. In delivering the radiation, assumptions are made that the artery is linear and that the radiation is distributed in a uniform manner. These assumptions, however, are often incorrect due to various factors, such as a curve in the artery which may result in a higher concentration of radiation being delivered at surfaces of the artery closest to the turn and lower concentrations being delivered at arterial surfaces farther away from the turn. Because of difficulty in controlling the rotational orientation of a catheter, conventional techniques are unable to optimally deliver a dose to a lesion.
One obstacle to the optimal delivery of a dose is the inability to detect the rotational position of the catheter. With many catheters, it is impossible to ascertain the rotational position of the catheter within the patient. U.S. Pat. No. 5,054,492 to Scribner et al. and U.S. Pat. No. 5,596,990 to Yock et al., the disclosures of which are both incorporated herein by reference, are directed to this problem but offer incomplete solutions. Scribner and Yock disclose catheter guides having a marker that serves as a landmark. With Scribner, an ultrasonic catheter is equipped with an ultrasonically opaque marker which appears as an artifact on resultant images taken with the transducer. The catheter also has a fluoroscopic marker that is used to identify the rotational position of the catheter from which the orientation of the ultrasonic marker may be deduced. Yock relates to a catheter having an ultrasonic catheter having a marker that is placed at a predetermined orientation and an image of the marker is produced.
Although Scribner and Yock offer improvements in that they provide some reference to estimate orientation, these references provide an initial orientation but do not allow the precise orientation of the catheter to be determined at all locations along a treatment volume. Since the catheter may twist or turn as it is being moved along the treatment volume, the initial indication of orientation provided by the marker may lead clinicians to an incorrect assumption about the orientation of the catheter. Scribner and Yock, moreover, do not assist clinicians in their estimate of the catheter's position along the length of a treatment volume. A need therefore still exists for devices and methods that enable the precise determination of a catheter's location and orientation.